Spectrum of Melioidosis in the Suburbs of Mangalore, S West Coast of India

SPECTRUM OF MELIOIDOSIS IN THE SUBURBS OF MANGALORE, S WEST COAST OF INDIA

Beena Antony, Hilda Pinto, Meena Dias, Anup Kumar Shetty, Bibin Scaria, Thomas Kuruvilla and Rekha Boloor

Department of Microbiology, Father Muller Medical College, Kankanady, Mangalore, Karnataka State, India

Abstract. Melioidosis is an emerging infection in India. Seventeen cases of culture proven melioidosis are reported in this study. The isolation rate was high during the rainy season. Except one case, all the patients had diabetes mellitus as an underlying disease. Eleven patients improved with ceftazidime or combination therapy and maintenance therapy with doxycycline and Cotrimoxazole. The high prevalence of B. pseudomallei in this region is a matter for serious concern. Key words: Burkholderia pseudomallei, melioidosis

INTRODUCTION stagnant water, rice farming areas, rubber plantations, irrigated agricultural sites, Burkholderia pseudomallei, the caus- drains and ditches (Raja et al, 2005). It has ative agent of melioidosis was first re- also emerged as a major veterinary patho- ported by Captain Alfred Whitmore and gen. B. pseudomallei has been described as his assistant Krishnaswami at Rangoon a ‘Vietnamese time bomb’ and is consid- General Hospital, Burma in 1911 (White, ered as a potential biological weapon 2003). The name melioidosis is derived (White, 2003). The name of this organism from the Greek word ‘melis’, meaning ‘dis- has undergone many systematic revisions temper of asses’ and ‘edios’, meaning ‘re- to obtain the present nomenclature. The semble’ (Raja et al, 2005). Melioidosis is previous nomenclatures includes Bacillus widespread in Southeast Asian countries pseudomallei, Bacillus whitmori, Pfefferella and northern Australia. The clinical pre- pseudomallei and Pseudomonas pseudomallei. sentation varies from a short febrile illness Based on rRNA homology, the organism to prolonged fever with or without lym- has now been assigned to the genus phadenitis, mimicking tuberculosis. It Burkholderia (Gilardi, 1991). causes localized acute or chronic suppu- The first case was reported in india in rative infections in internal organs lead- 1991, in Dapoli Taluk of Maharashtra ing to fatal septicaemia (White, 2003) B. (Raghavan et al, 1991). There have been pseudomallei is a saprophyte in the soil, many reports from various parts of India, Correspondence: Dr Beena Antony, Depart- including coastal Karnataka (Sengupta et ment of Microbiology, Father Muller Medical al, 1998; Rao and Shivananda 1999; College, Kankanady, Mangalore, Karnataka Kanungo et al, 2002; Dias et al, 2004; State, India. Vidyalakshmi et al, 2007; Mukhopadhyay Tel: +91 824 2238273; Fax: +91 824 2437402 et al, 2008). Despite disputes regarding the E-mail: [email protected] etiology of outbreaks of plague in

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Maharashtra and Gujarat in 1994, it is likely features including abscesses, septicemia , the etiology was B. pseudomallei (Bharadwaj pneumonia, glomerulonephritis and pyr- et al, 1994). exia (Table 1). In two cases, there were The present study reports a case se- slowly progressive granulomatous lesions ries at a tertiary care hospital in Mangalore, with central necrosis mimicking tubercu- a west coastal region of southern India. We lous osteomyelitis. report 17 cases of B. pseudomallei isolated Of 17 cases reported in the study, the from patients with various clinical mani- frequency of isolation was high during festations. June- September, which constituted the monsoon season ,with heavy rainfall in MATERIALS AND METHODS this region. Fourteen patients belonged to the coastal regions of Karnataka State and Seventeen patients with culture 3 from coastal regions of Kerala State. Of proven melioidosis were included in the these 17 cases, 12 were males and 5 were study. Motile gram-negative bacilli with females aged 34-65 years old. Seventy per- typical bipolar staining showing safety-pin cent of case were male. appearance, a positive cytochrome oxidase test, pink dry colonies on MacConkey’s Nine of the cases acquired the infec- agar, characteristic colony morphology on tion due to contact with contaminated soil Ashdown media (Ashdown, 1979) resis- through abrasions by agricultural expo- tant to gentamicin, polymyxin B and Colis- sure or gardening. The details of the pa- tin were presumptively identified as B. tients, clinical manifestations, predispos- pseudomallei, according to the screening ing factors and outcomes are described in profile devised by Dance et al (1989). De- Table 1. tailed characterization was done accord- Co-morbid conditions such as malig- ing to the standard procedures which in- nancy, acute respiratory distress syn- cludes: growth at 42ºC, production of cata- drome, renal failure, liver abscess were lase, oxidative utilization of glucose, lac- present in few of our patients. Pyrexia and tose, mannitol and maltose, liquefaction of non-disseminated septicemia were the gelatin, reduction of nitrate, hydrolysis of most frequent clinical findings in our arginine and inability to decarboxylate study. Chest involvement was very low in lysine (Jesudason et al, 1997; Koneman et this study. Except one patient, all the pa- al, 1997). The identification of initial 4 iso- tients had DM as an underlying disease. lates was confirmed at the Christian Medi- All the strains of B.pseudomallie isolated cal College, Vellore, Tamilnadu State, In- in this study were uniformly resistant to dia, a reference center for B. pseudomallei gentamicin, colistin, polymyxin B and and non-fermenters. Antimicrobial sus- showed variable resistance to cephalospor- ceptibility testing was performed by ins. All 17 strains were sensitive to Kirby-Bauer method according to Clinical amoxicillin-clavulanic acid, ciprofloxacin, Laboratories Standard Institute (CLSI) Cotrimoxazole, doxycycline, chlorampheni- guidelines (2005). col and ceftazidime. Eleven patients improved with proper treatment (ceftazidime, RESULTS Co-trimoxazole, doxycycline), whereas 6 In the present study, the 17 cases de- expired in spite of treatment. All the recov- scribed here exhibited a variety of clinical ered patients were put on maintenance

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Table 1 Details of melioidosis cases documented in the study. Sl. Age in Sex Specimen Predisposing Clinical Duration Treatment Outcome No. years factors presentation of illness

162FPus DM Fever, cellulitis in 2 weeks CAZ, CIP Expired the neck, sepsis 248MPus DM Chronic osteomyelitis 1 month CAZ, CTX Recovered mimicking TB 355MPus DM, hepatitis Chronic osteomyelitis 1 month MEM, CTX Recovered mimicking TB 465MPus DM, epilepsy Parieto- occipital 1 year MEM Expired scalp abscess 545FPus DM Lateral chest wall 3 weeks CTX, AMC Recovered abscess 652MPus DM Fever, septic arthritis 3 weeks CAZ, CTX Recovered of hip, gluteal abscess, sepsis 765MPus Nil Submandibular abscess 10 days LVX, CTX Recovered 850FPus DM Cellulitis of the leg 2 months CAZ, CTX Recovered 941MBlood DM Fever, sepsis 2 months CAZ, CTX Recovered 10 55 M Blood DM, Fever, septicemia 1 month CFT, AKN Expired alcoholism septic arthritis hip, gluteal abscess 11 34 M Blood DM, Renal Fever, acute renal 2 months CAZ Improved impairment, failure, sepsis steroid therapy glomerulonephritis 12 42 M Blood DM Fever, septicemia 2 months PTZ Expired bilateral pneumonia, respiratory failure 13 55 M Blood DM, Fever, diabetic 1 month CFT, DOXY Discharged urine alcoholism gangrene of toe, against tuberculosis liver abscess, sepsis medical advice 14 61 M Blood DM Fever, sepsis 2 weeks CAZ, CTX Recovered multiloculated encysted pleural effusion 15 63 F Blood, DM, Fever, septicemia 1 month CEF Expired urine carcinoma respiratory failure, of lung renal failure 16 40 M Sputum DM Fever, chronic cough 1 month CAZ, CTX Recovered mimicking tuberculosis 17 50 F Pleural DM, Chronic Multiple liver abscess, 6 weeks CEF, Expired fluid UTI splenic abscess, pleural AKN, CIP effusion DM, Diabetes mellitus; F, Female; M, Male; CAZ, Ceftazidime ; CFT, Cefotaxime; CEF, Ceftriaxone; CTX, Cotrimoxazole; CIP, Ciprofloxacin; LVX, Levofloxacin; MEM, Meropenem; AKN, Amikacin; AMC, Amoxycillin- Clavulanic acid; DOXY, Doxycycline

Vol 41 No. 1 January 2010 171 SOUTHEAST ASIAN J TROP MED PUBLIC HEALTH therapy with doxycycline and Cotrimo- reported in Thailand), while genitourinary xazole for 2-3 months. infections and prostatic abscesses (commonly reported in Australia) were not com- DISCUSSION mon in this study (Vatcharapreechasakul et al, 1992; Cheng and Currie, 2005). In con- B.pseudomallei, an emerging pathogen trast to studies of melioidosis from other in India, is overlooked or under reported regions, chest involvement was found to be due to lack of awareness, low index of sus- only 8% in Mukhopadhyay et al (2008), 36% picion and morphological resemblance to in Vidyalakshmi et al (2007) and 23.5% in Pseudomonas species. Typical pink dry colo- the present study. These findings need to nies on MacConkey’s agar, due to the pro- be evaluated further. duction of oxalic acid from amino acids Except for one patient, all the patients and the alteration of pH (Shankar and Rao, in our study had DM as an underlying dis- 2005), a characteristic microscopic appear- ease (random blood sugar level ranging ance, a positive cytochrome oxidase test, from 200- 540 mg/dl at the time of admis- dry, wrinkled, purple colored colonies sion). A high incidence of DM has been with corrugated edges on Ashdown me- reported in other studies from this geo- dium and antimicrobial resistance pattern graphical region [76% by Vidyalakshmi will be helpful in the presumptive iden- et al (2007) and 56% by Mukhopadhyaya tification. Other media available for the se- et al (2008)]. Isolated case reports from lective isolation of B. pseudomallei are B. India also showed DM as a predisposing pseudomallei selective agar (BPSA) (Howard factor (Anuradha et al, 2003). India being and Inglis, 2003) and B. cepacia medium. the country with one of the greatest in- According to a recent study, sensitivity of cidence of diabetics of about 35 million detection of B. pseudomallei colonies on these (Ramachandran et al, 2004; Mohan et al, media remain the same, but the selectivity 2005), high incidence of diabetes seen of BPSA was lower than the other two me- in this study is not surprising. Hence it dia (Peacock et al, 2005). would seem appropriate to further evalu- Heavy rainfall, damp soil, proximity to ate Pseudomonas-like organisms cultured agricultural land in this region, occupa- from diabetic patients to rule out the pres- tional contact during agriculture have been ence of B. pseudomallei. contributing factors for infection with B. The recommended treatment regimen pseudomallei. The fact that a large popula- for melioidosis is 10-14 days of ceftazidime tion in India is exposed to the agricultural or meropenem or imipenem with or with- land and direct contact with wet soils is a out Cotrimoxazole, and eradication matter of concern. Nine of these cases ac- therapy is 3 months with Cotrimoxazole quired the infection due to contact with with or without doxycycline (Currie, contaminated soil. Melioidosis mainly af- 2005). Eleven patients improved with fects people who have underlying diabe- treatment (ceftazidime, Cotrimoxazole, and tes mellitus (DM), renal disease, alcoholism, doxycycline), whereas 6 expired in spite of cirrhosis, chronic lung disease, or immuno- treatment. Treatment of B. pseudomallei is a suppression by chronic disease or drugs. challenge since it can survive intracellularly The present findings are consistent with and can produce biofilms and microcolo- previous studies. Two patients had mul- nies sheltered from beta-lactam drugs tiple liver and splenic abscess (commonly (Pruksachartvuthi et al, 1990). A combina-

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